The immunological aspects of chronic viral infections in man and animals have been well studied, but little is known about those properties of the infectious agents per se which establish persistence. Since defective-interfering (DI) virus particles have been shown to regulate virus synthesis in vitro, and in vivo regulatory role is highly suggested and should be investigated. The most manipulable model system with which to study this phenomenon is the murine-lymphocytic choriomeningitis virus system. I propose to purify standard and DI LCMV for the purposes of characterizing the RNA and protein. I will examine the therapeutic, prophylactic, and regulatory effects of the DI virus on the course of the LCMV chronic and acute infections. Using microtiter techniques, I will determine the effects of DI virus on individual cells challenged by standard virus, and using clones of neuroblastoma cell lines, I will quantitate the effects of DI virus infection on neuronal enzymes and correlate these results to enzyme levels found in infected mouse brains. The functions and properties of acutely vs. persistently infected macrophages will be examined, using cells taken directly from mice. I will attempt to extract biologically active DI virus from infected mouse tissue and determine whether DI virus is the main antigen (because of its bulk) of the immune response. Cell lines isolated from strains of mice with different sensitivities to LCMV will be tested for their propensity toward production of DI virus. The fate and distribution of labeled purified virus and viral-antibody complexes injected into mice will also be examined. The effects of DI virus on the modulation of viral cell surface antigens will be quantitated. By these experiments, I hope to discover the role of DI virus on the regulation of virus titers and its contribution to the pathology of in vivo chronic infections. BIBLIOGRAPHIC REFERENCES: Welsh, R.M., Lampert, P.A. Burner and M.B.A. Oldstone. Antibody-complement interactions with purified lymphocytic choriomeningitis virus. Virology, in press, l976. Welsh, R.M., F.C. Jensen, N.R. Cooper and M.B.A. Oldstone. Inactivation and lysis of oncornaviruses by human serum. Virology, in press, l976.